Investigating Systemic and Local Vascular Responses to Apelin in the Context of Renin-angiotensin Upregulation

University of Edinburgh12 enrolled

Overview

The apelin-APJ system is a relatively new discovery. It has generated interest in part due to it's apparent ability to counteract the renin-angiotensin system, which is frequently overactive in many cardiovascular disease. Two of the main actions of apelin are to increase the pumping ability of the heart and cause blood vessels to relax. The investigators wish to assess if these actions are altered in the setting of normal renin-angiotensin activation and increased renin-angiotensin activity.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Heart Disease Heart Failure Vasodilatation

Interventions

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial apelin infusions at 0.3, 1.0 and 3.0 nanomol/ml.

AcetylcholineDRUG

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 5, 10 and 20 microg/min

Sodium nitroprussideDRUG

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 1, 2 and 4 microg/min

Systemic apelin infusionDRUG

Following plethysmography patients will receive systemic infusion of (Pry)Apelin-13 (30, 100 and 300 nmol/min) for 5 mins cardiac output, blood pressure, heart rate and systemic vascular resistance will be measured at 5-min intervals.

Eligibility

Sex: ALLMin age: 18 MonthsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * \>18yr Exclusion Criteria: * Lack of informed consent * Age \< 18 years, * Current involvement in other research studies, * Systolic blood pressure \>190 mmHg or \<100 mmHg * Malignant arrhythmias * Renal or hepatic failure * Haemodynamically significant aortic stenosis * Severe or significant co morbidity * Women of childbearing potential. * Any regular medication * Previous history of any cardiovascular disease

Locations (1)

Clincial Research Facility, Royal Infirmary of Edinburgh, 51 Little France Cresc

Edinburgh, United Kingdom

Outcomes

Primary Outcomes

Change in cardiac output

Time frame: 12 months

Change in apelin mediated vasodilatation

Time frame: 12 months

Secondary Outcomes

Change in systemic haemodynamics

Time frame: 12 months

Change in relevant neurohumoral hormones

Time frame: 12 months

Data from ClinicalTrials.gov

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